De novo adipocyte differentiation from Pdgfrβ+ preadipocytes protects against pathologic visceral adipose expansion in obesity

Mengle Shao, Lavanya Vishvanath, Napoleon C. Busbuso, Chelsea Hepler, Bo Shan, Ankit X. Sharma, Shiuhwei Chen, Xinxin Yu, Yu A. An, Yi Zhu, William L Holland, Rana K Gupta

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Pathologic expansion of white adipose tissue (WAT) in obesity is characterized by adipocyte hypertrophy, inflammation, and fibrosis; however, factors triggering this maladaptive remodeling are largely unknown. Here, we test the hypothesis that the potential to recruit new adipocytes from Pdgfrβ+ preadipocytes determines visceral WAT health in obesity. We manipulate levels of Pparg, the master regulator of adipogenesis, in Pdgfrβ+ precursors of adult mice. Increasing the adipogenic capacity of Pdgfrβ+ precursors through Pparg overexpression results in healthy visceral WAT expansion in obesity and adiponectin-dependent improvements in glucose homeostasis. Loss of mural cell Pparg triggers pathologic visceral WAT expansion upon high-fat diet feeding. Moreover, the ability of the TZD class of anti-diabetic drugs to promote healthy visceral WAT remodeling is dependent on mural cell Pparg. These data highlight the protective effects of de novo visceral adipocyte differentiation in these settings, and suggest Pdgfrβ+ adipocyte precursors as targets for therapeutic intervention in diabetes.

Original languageEnglish (US)
Article number890
JournalNature Communications
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2018

Fingerprint

obesity
adipose tissues
White Adipose Tissue
Adipocytes
Intra-Abdominal Fat
Obesity
Tissue
expansion
Tissue Expansion
homeostasis
Adipogenesis
fibrosis
diets
Adiponectin
regulators
fats
High Fat Diet
Nutrition
Medical problems
cells

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

De novo adipocyte differentiation from Pdgfrβ+ preadipocytes protects against pathologic visceral adipose expansion in obesity. / Shao, Mengle; Vishvanath, Lavanya; Busbuso, Napoleon C.; Hepler, Chelsea; Shan, Bo; Sharma, Ankit X.; Chen, Shiuhwei; Yu, Xinxin; An, Yu A.; Zhu, Yi; Holland, William L; Gupta, Rana K.

In: Nature Communications, Vol. 9, No. 1, 890, 01.12.2018.

Research output: Contribution to journalArticle

Shao, M, Vishvanath, L, Busbuso, NC, Hepler, C, Shan, B, Sharma, AX, Chen, S, Yu, X, An, YA, Zhu, Y, Holland, WL & Gupta, RK 2018, 'De novo adipocyte differentiation from Pdgfrβ+ preadipocytes protects against pathologic visceral adipose expansion in obesity', Nature Communications, vol. 9, no. 1, 890. https://doi.org/10.1038/s41467-018-03196-x
Shao, Mengle ; Vishvanath, Lavanya ; Busbuso, Napoleon C. ; Hepler, Chelsea ; Shan, Bo ; Sharma, Ankit X. ; Chen, Shiuhwei ; Yu, Xinxin ; An, Yu A. ; Zhu, Yi ; Holland, William L ; Gupta, Rana K. / De novo adipocyte differentiation from Pdgfrβ+ preadipocytes protects against pathologic visceral adipose expansion in obesity. In: Nature Communications. 2018 ; Vol. 9, No. 1.
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